HIV protease inhibitors are highly potent agents that inhibit the replication of HIV (human immunodeficiency) viruses and prolong the lives of individuals infected with HIV. Because of the hydrophobic nature of the active site of HIV protease, most HIV protease inhibitors are relatively lipophilic and poorly soluble. Consequently, the delivery of adequate amounts of protease inhibitors to provide antiviral efficacy often requires multiple capsules or tablets. Some protease inhibitors such as ritonavir are not absorbed in the solid state, and often require formulations to solubilize the drug substance.
In addition to being an effective inhibitor of HIV protease, ritonavir is also effective in inhibiting cytochrome P450 monooxygenase. Co-administration of ritonavir with a HIV protease inhibitor that is metabolized by cytochrome P450 monooxygenase often results in improvement in pharmacokinetics (i.e. increased half-life and increased blood levels, particularly increased minimum or trough concentration) of such HIV protease inhibitor. The co-formulated mixture of lopinavir and ritonavir has been shown to be a potent HIV protease inhibitor regimen. Currently, lopinavir/ritonavir is dosed twice daily at 400/100 mg, respectively, co-formulated as a solution in three soft elastic capsules. The three capsules are required because of the limited solubility of lopinavir and ritonavir, and the need for dosing as a solution.
Such solution formulations often result in high pill burdens and poor patient compliance. There is therefore a need for technologies that can provide good oral absorption from formulations with higher drug load per unit dosage.